The needs to efficiently deliver genetic cargo and to maintain long-term transgene expression in vivo prompted the development of the HIV-1 based vector system. The novel HIV-1 based vectors, devoid of sequences encoding any of the HIV-1 proteins, proved efficient at transducing various tissues in vivo (brain, liver, muscle, retina, and hematopoietic stem cells) without any detectable pathology. However, it is clear that further improvements in: vector production, transgene expression and regulation, better characterization of the mechanisms involved in vector integration, and the development of immune response against vector delivered transgenes are required before HIV-1 vectors are considered safe and efficacious enough for human clinical trials. Our lab is focused on the development of HIV-1 vectors for gene therapy of genetic diseases such as hemophilia A and B, as well as well as a means of treating prostate cancer. In addition, we are using the vector system to study HIV-1 biology. Specifically, we characterize the mechanism of vector integration into the host cell genome and the risks of insertional mutagenesis involved in this process. In parallel, we develop non-integrating HIV-1 vectors; to this end, we investigate the effects of DNA repair pathways on the formation of episomal HIV-1 vector forms and the mechanisms, which down regulate transgene expression from non-integrated vectors.

We are also interested in utilizing the HIV-1 vector system for functional genomic applications. Recently, we have developed a novel lentiviral vector, which facilitates high throughput gene-function screening of cDNAs. To facilitate the generation of transgenic animals by retroviral vectors, we investigate the mechanism that renders lentiviral vectors resistant to transcriptional silencing in the early mouse embryo.